Our objective is to define in genetic and molecular terms the mechanisms which regulate the expression of genetic information during cell growth and development. For this purpose, we are investigating two model systems which serve as analogs for erythrodifferentiation and immunodifferentiation. This work has led to the development of techniques for gene isolation and a successful vector system and strategy for cloning virtually any detectable mammalian gene using recombinant DNA technology. Initial experiments led to the cloning of several mouse globin and immunoglobulin genes and to the demonstration that structural eukaryotic genes were encoded in discontinuous blocks interrupted by intervening sequences of DNA. It was further demonstrated that these intervening sequences were transcribed into an mRNA precursor from which they must be edited for translation. Examination of the immunoglobulin cloned genes led to the proposal of a recombination model for the generation of antibody diversity.